He was in decent form over the first four innings before the Astros turned on a few floating knuckleballers and built a lead that was too much for the Blue Jays to overcome.
Dickey gave up a two-run homer to Robbie Grossman in the fifth inning and a three-run shot to Jonathan Villar in the seventh as Toronto missed a chance for a three-game sweep by dropping a 6-4 decision to Houston at Rogers Centre.
"It's a real surprise when I have a knuckleball like that and have the outcome that we had," Dickey said.
Jason Castro added a solo shot in the eighth inning off reliever Esmil Rogers to help send Toronto (5-5) back to the .500 mark. Colby Rasmus hit a solo homer for the Blue Jays, who scratched out three runs in the bottom of the ninth to make a game of it.
"We're disappointed, but they outplayed us," said Toronto manager John Gibbons.
Dickey (1-2) allowed five earned runs, three walks and six hits over seven innings. He said he was pleased with the speed and action on his knuckleball.
"It was moving so much, I was throwing it hard, it felt great out of my hand," Dickey said. "And then we just had a couple of hiccups and it happened really quickly."
Starter Dallas Keuchel (1-1), meanwhile, was sharp for Houston (4-6). He went seven innings and allowed five hits and one earned run.
"He really showed it tonight against a really good hitting lineup," said Astros manager Bo Porter. "He was outstanding."
Keuchel has now gone at least seven innings in each of his three career starts against Toronto.
"Those guys that have got a little finesse, a little command, they have a tendency to give us problems," Gibbons said.
Toronto brought the potential tying run to the plate in the ninth but Maicer Izturis hit a comebacker to Anthony Bass, who recorded the one out for his first save.
Leadoff man Melky Cabrera doubled in the first inning to extend his hitting streak to 10 games. He moved to third on a sacrifice bunt but was left stranded when Jose Bautista popped up and Edwin Encarnacion grounded out.
Castro led off the fourth inning with a sharp single to centre field for the Astros' first hit of the game. He was forced out at second base when Jose Altuve hit into a fielder's choice.
Dickey caught Altuve leaning towards second base on a leadoff and picked him off for the second out before fanning Chris Carter.
Marc Krauss led off the fifth with a double off the wall in right-centre field and moved to third when Matt Dominguez grounded out to first base. Grossman turned on a 3-0 pitch for his first homer of the season.
Dominguez made a stellar defensive play in the fifth inning to rob Brett Lawrie of Langley, B.C., of a sure hit. The Houston third baseman dived to his left and threw from his knees to get the speedy Canadian by a half-step.
Rasmus followed with a solo homer that hit the facing of the second level in right-centre field. It was his first home run of the season.
Gibbons challenged a call later in the frame when Cabrera was called out at first base. Cabrera stumbled out of the batter's box and Dominguez bobbled the ball at third base before recovering to fire a throw that was barely in time at first.
The umpires reviewed the play and the original call stood to end the inning.
In the seventh, Dominguez hit a one-out double and Grossman walked. After a visit to the mound by pitching coach Pete Walker, Villar crushed Dickey's first pitch to deep centre for his second homer of the season.
Astros reliever Josh Fields gave up two runs in the ninth when pinch-hitter Adam Lind doubled to the gap in left-centre field. Lind scored when Bass made a throwing error to first.
Houston is expected to be one of the lesser lights in the American League West this season. However, the Astros have shown some pop early on with 14 homers in their first 10 games.
"This game, it can be cruel," Dickey said. "It doesn't matter if you're the New York Yankees or the Houston Astros. There's big-league ball players on the other side of that diamond and if you leave a ball over the middle of the plate, they're going to hit it.
"It doesn't matter who they are."
Notes: Both teams had eight hits. ... Announced attendance was 15,778. ... Cabrera went 2-for-5 to improve his batting average to .333. Former Blue Jays slugger Vernon Wells owns the team's season-opening hit streak record of 12 games in 2006. ... The game took two hours 49 minutes to play. ... Blue Jays reliever Steve Delabar was not available after taking a liner off the leg in Wednesday night's game. Gibbons said X-rays were negative and that Delabar was walking around and feeling good before the game. ... J.A. Happ allowed one run on four hits in 4 2/3 innings in a rehab start for the triple-A Buffalo Bisons on Thursday. The Blue Jays placed the left-hander on the disabled list March 30 due to lower back tightness. The Bisons dropped a 7-4 decision to the Pawtucket Red Sox. ... The Blue Jays will kick off a nine-game road trip against Baltimore on Friday night. Right-hander Dustin McGowan (0-1) is scheduled to start the opener of the three-game series against Orioles right-hander Chris Tillman (1-0).